WEEK 1: Inflammation of the bowel Flashcards
Define inflammatory bowel diseases.
It is comprised of two major disorders. State them.
Inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal (GI) system.
It is comprised of two major disorders: ulcerative colitis (UC) and Crohn disease (CD).
Describe Crohn disease (CD).
Crohn disease
-Mediated by dysfunctional IL-23-Th17 signaling.
-Affects any part of the gastrointestinal disease
-It is both ulcerative and may also cause lumen narrowing.
-The pattern of inflammation in CD is discontinuous resulting in characteristic “skip lesions.”
*The early lesion is superficial ulcer in the GI mucosa.
Ulcers could be deep resulting in fissure formation.
Mucosal edema gives “cobblestone” appearance in GI mucosa.
*The inflammation is often transmural, penetrating to the muscularis or serosal layers of the GI tract.
*Complications such as strictures, fistulae, abscesses, and perforation are common in CD.
Discuss Ulcerative colitis.
ULCERATIVE COLITIS
*Mediated by Th2 cells
*Ulcerative colitis is limited to the colon and rectum.
*Extends only into the mucosa and submucosa.
*The lesions are continuous
Discuss the epidemiology of Inflammatory bowel disease.
*Both Crohn disease and ulcerative colitis frequently
present during adolescence or in young.
*In Western industrialized nations, IBD is most common
among whites and eastern European (Ashkenazi) Jews.
*This predilection is at least partly due to genetic factor
*The geographic distribution of IBD is highly variable, but
it is most prevalent in North America, Northern Europe,
and Australia
*The incidence of IBD worldwide is on the rise and it is
becoming more common in regions in which the
prevalence was historically low.
Discuss the hygiene hypothesis of asthma and extrapolate to IBD.
The hygiene hypothesis, first applied to asthma,
says that childhood and even prenatal exposure
to environmental microbes resets the immune
system in a way that prevents excessive reactions.
Extrapolated to IBD, it suggests that a reduced frequency of enteric infections due to improved hygiene has resulted in inadequate development of regulatory processes that limit mucosal immune responses early in life.
What do most investigators believe that IBD results from?
In Crohn disease, what is the concordance rate (%) for monozygotic twins?
What is the concordance of monozygotic twins for ulcerative colitis?
What is the conclusion from the 2 values?
Most investigators believe that IBD results from the combined effects of alterations in host interactions with intestinal microbiota, intestinal epithelial dysfunction, aberrant mucosal immune responses, and altered composition of the gut microbiome.
Risk for disease is increased when there is an affected family member.
In Crohn disease, the concordance rate for monozygotic twins is approximately 50% while the concordance of monozygotic twins for ulcerative colitis is only 16%, suggesting that genetic factors are less dominant in this form of IBD.
Mucosal immunity contributes to the pathogenesis of ulcerative colitis and Crohn disease are still being deciphered, immunosuppressive and immunomodulatory agents remain mainstays of IBD therapy.
Discuss the pathogenesis of IBD.
Polarization of helper T cells to the TH1 type is well recognized in Crohn disease, and some data suggest that TH17 T cells also contribute to disease pathogenesis.
Defects in regulatory T cells, especially the IL-10-producing
subset, are believed to underlie the inflammation especially in Crohn disease.
* Epithelial defects. A variety of epithelial defects have been described in Crohn disease, ulcerative colitis, or both.
Microbiota. The quantity of microbial organisms in the
gastrointestinal lumen is enormous, amounting to as many as 1012 organisms/mL of fecal material in the colon (50% of fecal mass).
One model that unifies the roles of intestinal microbiota, epithelial function, and mucosal immunity suggests a cycle by which transepithelial flux of luminal bacterial components activates innate and adaptive immune responses.
In a genetically susceptible host, the subsequent
release of TNF and other immune signals directs epithelia to increase tight junction permeability, which further increases the flux of luminal material.
These events may establish a self-amplifying cycle in
which a stimulus at any site may be sufficient to initiate IBD
Describe the morphology of Crohn’s disease.
Crohn disease, also known as regional enteritis, may
occur in any area of the gastrointestinal tract but the
most common sites involved at presentation are the
terminal ileum, ileocecal valve, and cecum.
The presence of multiple, separate, sharply delineated
areas of disease, resulting in skip lesions, is
characteristic of Crohn disease and may help in
differentiation from ulcerative colitis.
The earliest lesion, the aphthous ulcer, may progress,
and multiple lesions often coalesce into elongated,
serpentine ulcers oriented along the axis of the bowel.
Edema and loss of normal mucosal folds are common.
Sparing of interspersed mucosa results in a coarsely
textured, cobblestone appearance in which diseased tissue is depressed below the level of normal mucosa.
Fissures frequently develop between mucosal folds and
may extend deeply to become sites of perforation or
fistula tracts.
The intestinal wall is thickened as a consequence of
transmural edema, inflammation, submucosal fibrosis,
and hypertrophy of the muscularis propria, all of which
contribute to stricture formation.
In cases with extensive transmural disease, mesenteric
fat frequently extends around the serosal surface
(creeping fat)
The microscopic features of active Crohn disease
include abundant neutrophils that infiltrate and
damage crypt epithelium.
Clusters of neutrophils within a crypt are referred to as
a crypt abscess and often are associated with crypt destruction.
Ulceration is common in Crohn disease, and there may be an abrupt transition between ulcerated and normal mucosa..
Noncaseating granulomas a hallmark of Crohn disease,
are found in approximately 35% of cases and may arise in areas of active disease or uninvolved regions in any layer of the intestinal wall.
Granulomas also may be found in mesenteric lymph nodes.
The absence of granulomas does not preclude a
diagnosis of Crohn disease.
Outline the Clinical Features of Crohn disease.
The clinical manifestations of Crohn disease are
extremely variable.
In most patients, disease begins with intermittent attacks of relatively mild diarrhea, fever, and abdominal pain.
Approximately 20% of patients present acutely with
right lower-quadrant pain and fever, which may mimic acute appendicitis or bowel perforation.
Patients with colonic involvement may present with
bloody diarrhea and abdominal pain, creating a
differential diagnosis with some colonic infections.
Iron-deficiency anemia may develop in individuals with colonic disease, while extensive small-bowel disease may result in serum protein loss and hypoalbuminemia, generalized nutrient. malabsorption, or malabsorption of vitamin B12 and bile salts.
Fibrosing strictures, particularly of the terminal ileum, are
common and require surgical resection.
Fistulas develop between loops of bowel and may also involve the urinary bladder, vagina, and abdominal or perianal skin.
Perforations and peritoneal abscesses can also occur.
Extraintestinal manifestations of Crohn disease include uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, and clubbing of the fingertips.
Ulcerative colitis always involves the rectum and extends proximally in a continuous fashion to involve part or the entire colon that can be diffusely ulcerated.
Skip lesions are not seen (although focal appendiceal or cecal inflammation occasionally may be present in those with left-sided disease).
What is the disease of the entire colon is termed?
What is the disease limited to the rectum or rectosigmoid referred to as?
Disease of the entire colon is termed pancolitis.
Disease limited to the rectum or rectosigmoid may be referred to descriptively as ulcerative proctitis or ulcerative proctosigmoiditis.
On gross evaluation, involved colonic mucosa may be slightly red and granular-appearing or exhibit extensive broad-based ulcers.
The transition between diseased and uninvolved colon can be abrupt.
Discuss morphology of ulcerative colitis.
Ulcers are aligned along the long axis of the colon but typically do not replicate the serpentine ulcers of Crohn disease.
Isolated islands of regenerating mucosa often bulge into the lumen to create small elevations, termed pseudo polyps.
Chronic disease may lead to mucosal atrophy and a flat, smooth mucosal surface lacking normal folds.
Unlike in Crohn disease, mural thickening is absent, the serosal surface is normal, and strictures do not occur.
inflammation and inflammatory mediators can damage the muscularis propria and disturb neuromuscular function leading to colonic dilation and toxic megacolon, which carries a significant risk for perforation.
Histologic features of mucosal disease in ulcerative colitis are similar to those in colonic Crohn disease and include inflammatory infiltrates, crypt abscesses, crypt distortion, and epithelial metaplasia.
However, skip lesions are absent, and inflammation generally is limited to the mucosa and superficial submucosa.
This distinction may not be demonstrated by endoscopic biopsies, which typically sample the mucosa and little or no
submucosa.
Granulomas are not present.
Some extraintestinal manifestations of ulcerative colitis overlap with those of Crohn disease, including migratory polyarthritis, sacroiliitis, ankylosing spondylitis, uveitis, skin lesions, pericholangitis, and primary sclerosing cholangitis.
Describe clinical features of ulcerative colitis.
Ulcerative colitis is a relapsing disorder characterized by
attacks of bloody diarrhea with expulsion of stringy, mucoid
material and lower abdominal pain and cramps that are temporarily relieved by defecation.
These symptoms may persist for days, weeks, or months before they subside, and occasionally the initial attack may be severe enough to constitute a medical or surgical emergency.
More than half of patients have mild disease, but almost all experience at least one relapse during a 10-year period.
Colectomy cures intestinal disease, but extraintestinal manifestations may persist.
What is one of the most feared long-term complications of ulcerative colitis and colonic Crohn disease.
Describe how the complication comes about?
Outline the risk for development of dysplasia.
What is done to facilitate early detection of neoplasia?
This process begins as dysplasia, which, just as in Barrett esophagus and
chronic gastritis, is a step along the road to full-blown carcinoma.
This process begins as dysplasia, which, just as in Barrett esophagus and chronic gastritis, is a step along the road to full-blown carcinoma.
The risk for development of dysplasia is related to several factors:
Duration of disease. Risk increases beginning 8 to 10 years after disease initiation.
* Extent of involvement. Patients with pancolitis are at greater risk than those with only left-sided disease.
inflammation (characterized by the presence of neutrophils) may increase risk.
This is another example of the enabling effect of inflammation on carcinogenesis.
To facilitate early detection of neoplasia, patients typically are enrolled in surveillance programs approximately 8 years after diagnosis of IBD.
Involvement of colon by ulcerative colitis
What part of the colon are affected by the following in ulcerative colitis?
*Right sided disease
*Left sided disease
*Proctosigmoiditis
*Proctitis
*Pancolitis
*Right sided disease: Ascending colon
*Left sided disease: Descending colon
**Proctosigmoiditis: Sigmoid colon + rectum
*Proctitis: rectum
*Pancolitis: entire colon
